{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T11:40:23Z","timestamp":1776685223889,"version":"3.51.2"},"update-to":[{"DOI":"10.12688\/f1000research.27952.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000}}],"reference-count":80,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Indonesian Ministry of Research, Technology and Higher Education","award":["11\/PPK\/E\/E4\/2018"],"award-info":[{"award-number":["11\/PPK\/E\/E4\/2018"]}]},{"name":"Ctech Labs Edwar Technology"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    <ns3:bold>Background:<\/ns3:bold>\n                    Breast cancer is the most common cancer in women worldwide and is the leading cause of death amongst women with cancer. One novel therapy used for breast cancer treatment\u00a0constitutes non-contact electric fields and is called electro-capacitive cancer therapy (ECCT) with intermediate frequency and low intensity. The objective of this study was to examine the effect of ECCT on mammary tumors growth in rats and observing the immune responses that play a role in fighting the tumor.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Methods:<\/ns3:bold>\n                    Female SD rats were used and divided into four groups, namely control (NINT), placebo (NIT), non- therapy (INT), and therapy (IT) groups with 6 biological replicates in each group. Rats in INT and IT groups were treated with 7,12-dimethylbenz[a]anthracene for mammary tumor induction. Only rats in NIT and IT groups were exposed to ECCT individually for 10 hours per day for 21 days. The size of all tumors was measured with a digital caliper. The distributions of PCNA, ErbB2, caspase-3, CD68, CD4, and CD8-positive cells were observed with immunohistochemistry and scoring with ImageJ.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Results:<\/ns3:bold>\n                    The growth rate of mammary tumors in IT group was significantly lower (p&lt;0.05) than that in INT group. The number of mitotic figures and the percentage of PCNA, caspase-3, and CD68-positive cells in IT group were significantly lower (p&lt;0.05) than those in INT group. Conversely, the percentage of CD8-positive T cells in IT group was significantly higher (p&lt;0.05) than that in INT group. Moreover, the CD4\/CD8 ratio in IT group was found to have decreased. Some tumor tissues were blackened and detached from the surrounding tissue, resulting in an open wound which then healed upon exposure.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Conclusions:<\/ns3:bold>\n                    Non-contact electric fields exposure showed inhibition on mammary tumor growth in rats while inducing CD8+ T cells, leading to tumor cell death and potentially helping wounds heal.\n                  <\/ns3:p>","DOI":"10.12688\/f1000research.27952.2","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T10:35:23Z","timestamp":1620124523000},"page":"35","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Cytotoxic T cells response with decreased CD4\/CD8 ratio during mammary tumors inhibition in rats induced by non-contact electric 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Alamsyah","year":"2020"}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/10-35\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/10-35\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/10-35\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:10:35Z","timestamp":1663200635000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/10-35\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,4]]},"references-count":80,"URL":"https:\/\/doi.org\/10.12688\/f1000research.27952.2","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.55837.r84419","asserted-by":"subject"},{"id-type":"doi","id":"10.3410\/f.740054704.793592350","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.55837.r84419","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,4]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/10-35\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.55837.r84419, Bilgin Keserci, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia, 21 May 2021, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/10-35\/v2#referee-response-84419","order":0,"name":"referee-response-84419","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.30917.r79324, Elfahmi Elfahmi, School of Pharmacy, Bandung Institute of Technology, Bandung, Indonesia, 03 Mar 2021, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/10-35\/v1#referee-response-79324","order":1,"name":"referee-response-79324","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Firman Alamsyah<\/b>; \n<i>Posted: 30 Mar 2021<\/i>; 1.&nbsp;The deviation value that is quite large in some data shows a quite different response from each individual rat to the electric field exposure. For example, in the SGR data (Figure 2), there is indeed 1 outlier data in each of the IN and INT groups. This may occur because the estrous cycle that stimulates prolactin can be different in each individual mouse which can affect differences in the growth rate of mammary tumors in rat (Nandi et al., 1995; Schedin et al., 2000). In addition, different levels of stress due to therapy in individual cages could affect differences in the development of mammary tumors in individual rat (Hermes et al., 2009; De la Roca-Chiapas, et al., 2016). We have added this argument in the revision of our article.  2.&nbsp;We have explained the safety of electric field of ECCT to mammry and skin tissues of animal models in the second&nbsp;paragraph of the Introduction as reported in our previous publication. In addition, ECCT has passed the phase I clinical trials for healthy volunteers as stated in the last sentence of the Discussion. The safety of ECCT in normal tissue is determined by the membrane potential of the tissue which is higher than that in cancer cells (Yang and Brackenburry, 2013; Kadir et al., 2018). External electric field exposure cannot penetrate normal cell membranes due to the higher membrane potential (Kirson et al., 2004; Yang and Brackenburry, 2013; Kadir et al., 2018) and only causes rotational motion of the cell organelles (Kirson et al., 2004). On the other hand, external electric field exposure can penetrate cancer cell membranes with lower cell membrane potential, thereby interfering with mitosis (Kirson et al., 2004; Yang and Brackenburry, 2013; Kadir et al., 2018). However, not all normal cells have a higher membrane potential than cancer cells. For example, liver cell has the same membrane potential as MCF-7 cancer cell (Yang and Brackenburry, 2013; Kadir et al., 2018). &nbsp;Even so, we found that liver function was not impaired based on alanine transferase activity and bilirubin levels in blood plasma. The data of the safety of ECCT exposure in rat and healthy volunteers will be published separately this year.  3.&nbsp;We have tried various frequencies (100, 150, and 200 kHz) and intensities (10 Vpp, 18 Vpp and 30 Vpp) of the ECCT electric field in preclinical studies and found that a frequency of 100 kHz and an intensity of 18 Vpp are the optimum electric field exposure for breast cancer therapy.  4.&nbsp;ECCT toxicity data on the liver, kidney and hematological profiles will be published separately this year.","URL":"https:\/\/f1000research.com\/articles\/10-35\/v2#referee-comment-6519","order":2,"name":"referee-comment-6519","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This study was funded by Ctech Labs Edwar Technology for the in vivo experiment and a grant from the Indonesian Ministry of Research, Technology and Higher Education (Contract number: 11\/PPK\/E\/E4\/2018) to RP for the immunohistochemistry application. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}